Keap1 Blocking Peptide for STJ506354 is synthetically produced from the 500-550 sequence and is suitable for use in western blot applications.
Applications
Immunodepletion/Immunocompetition
Note
STRICTLY FOR FURTHER SCIENTIFIC RESEARCH USE ONLY (RUO). MUST NOT TO BE USED IN DIAGNOSTIC OR THERAPEUTIC APPLICATIONS.
Product Properties
Formulation
Liquid form at 2.5mg/ml concentration in PBS. Up to 5% DMSO can be added. Orders with >1mg can be supplied in lyophilized powder form, or in buffer of choice.
Storage Instruction
Store at-20°C for long term storage. Avoid freeze-thaw cycles.
This blocking peptide is recommended for use in combination with Keap1 antibody, STJ506354
Additional Info
Tissue Specificity
Broadly expressed, with highest levels in skeletal muscle.
Post Translational Modifications
Non-enzymatic covalent modifications of reactive cysteines by electrophile metabolites inactivate the BCR(KEAP1) complex. Accumulation of fumarate promotes the formation of cysteine S-succination (S-(2-succinyl)cysteine), leading to inactivate the BCR(KEAP1) complex and promote NFE2L2/NRF2 nuclear accumulation and activation. Nitric oxide-dependent 8-Nitro-cGMP formation promotes cysteine guanylation (S-cGMP-cysteine), leading to NFE2L2/NRF2 nuclear accumulation and activation. Itaconate, an anti-inflammatory metabolite generated in response to lipopolysaccharide, alkylates cysteines, activating NFE2L2/NRF2. Methylglyoxal, a reactive metabolite that accumulates when the glycolytic enzyme PGK1 is inhibited, promotes formation of a methylimidazole cross-link between proximal Cys-151 and Arg-135 on another KEAP1 molecule, resulting in an inactive dimer that inactivates the BCR(KEAP1) complex. Degraded via a proteasomal-independent process during selective autophagy: interaction with phosphorylated SQSTM1/p62 sequesters KEAP1 in inclusion bodies, leading to its degradation. Auto-ubiquitinated by the BCR(KEAP1) complex. Quinone-induced oxidative stress, but not sulforaphane, increases its ubiquitination. Ubiquitination and subsequent degradation is most pronounced following prolonged exposure of cells to oxidative stress, particularly in glutathione-deficient cells that are highly susceptible to oxidative stress. Deubiquitinated by USP25.leading to stabilization.
Function
Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that regulates the response to oxidative stress by targeting NFE2L2/NRF2 for ubiquitination. KEAP1 acts as a key sensor of oxidative and electrophilic stress: in normal conditions, the BCR(KEAP1) complex mediates ubiquitination and degradation of NFE2L2/NRF2, a transcription factor regulating expression of many cytoprotective genes. In response to oxidative stress, different electrophile metabolites trigger non-enzymatic covalent modifications of highly reactive cysteine residues in KEAP1, leading to inactivate the ubiquitin ligase activity of the BCR(KEAP1) complex, promoting NFE2L2/NRF2 nuclear accumulation and expression of phase II detoxifying enzymes. In response to selective autophagy, KEAP1 is sequestered in inclusion bodies following its interaction with SQSTM1/p62, leading to inactivation of the BCR(KEAP1) complex and activation of NFE2L2/NRF2. The BCR(KEAP1) complex also mediates ubiquitination of SQSTM1/p62, increasing SQSTM1/p62 sequestering activity and degradation. The BCR(KEAP1) complex also targets BPTF and PGAM5 for ubiquitination and degradation by the proteasome.
Peptide Name
Kelch-Like Ech-Associated Protein 1Cytosolic Inhibitor Of Nrf2Inrf2Kelch-Like Protein 19
CytoplasmNucleusMainly CytoplasmicIn Response To Selective AutophagyRelocalizes To Inclusion Bodies Following Interaction With Sqstm1/P62
Alternative Peptide Names
Kelch-Like Ech-Associated Protein 1 proteinCytosolic Inhibitor Of Nrf2 proteinInrf2 proteinKelch-Like Protein 19 proteinKEAP1 proteinINRF2 proteinKIAA0132 proteinKLHL19 protein
